There are many diseases for which there are no vaccines and others for which the vaccines are not optimal or have significant side effects. The objectives of this project are to develop new vectors, characterize viral antigens, determine targets of humoral and cell mediated immunity, and use this information to develop candidate vaccines. Live recombinant viral vaccines, DNA vaccines and recombinant protein vaccines are being developed. Presently we are working on vaccinia virus-vectored vaccines for HIV. The vaccines are first tested in small animals and then in non-human primates. Phase 1 and 2 clinical trials with MVA-vectored vaccines developed in our laboratory are ongoing by collaborators. During FY2018, two phase 1 trials were completed and determined that the vaccines were safe and immunogenic. Animal studies revealed good boosting of MVA primed immunizations with gp140 and trimeric gp120 proteins and with virus-like particles.